Purpose: The purpose of this study is to determine whether hydroxyurea is safe and well tolerated at the two doses that will be examined alone and in combination with ddI, and whether there will be a more favorable antiviral effect when ddI and hyroxyurea are used in combination as compared to either one used as monotherapy Rationale Deoxyribonucleotide triphosphates (dNTPs) are the building blocks for cellular DNA and are synthesized de novo within the cell. Therefore, cellular DNA synthesis is dependent on the enzyme ribonucleotide reductase (RR), which catalyzes all four ribonucleotides to the reduced deoxy-form. HIV replication can be decreased by interfering with the concentration of dNTPs. Hydroxyurea inhibits RR activity and thus halts cellular DNA synthesis, and decreases the efficiency of HIV reverse transcription. This activity is synergistic with nucleoside RT inhibitor. In vitro testing shows greater synergy between hydroxyurea and DDI than with ZDV. Methods: This is a 24 week, phase I/II, randomized, double-blind, dose-ranging study in HIV-infected adults, whose CD4 lymphocyte count is between 200-500. There will be two 12-week treatment periods and 5 study arms. Pharmacokinetic monitoring will be performed on all subjects. Specimens for quantitative HIV RNA levels, CD4+/CD8+ lymphocyte counts, and dATP measurements will be obtained on weeks 2, 4, 8, 12 and 24. The initial 12-week portion of the study is designed to gather data that will be used to perform an antiretroviral activity analysis. The principal comparison used in the antiretroviral activity analysis will be between the hydroxyurea + ddI combination therapy arms and the ddI monotherapy arm. The Week 8 plasma HIV RNA levels will be used in this comparison. After the completion of Week 12, subjects on combination therapy will remain on their current therapy; and subjects on ddI monotherapy will remain on ddI and have hydroxyurea added at an assigned dose (1:1 randomization) of 1000 mg qd or 1500 mg qd. Randomization of subjects in the ddI monotherapy arm to low or high dose hydroxyurea + ddI combination therapy at Week 12 will have occurred at study entry. Therefore, all subjects will receive combination therapy during Weeks 12 to 24, with half receiving hydroxyurea at a dose of 1000 mg qd and half receiving hydroxyurea at a dose of 1500 mg qd. During Weeks 12 to 24, all study medication will be open label with no placebos. The following clinical and laboratory evaluations will be performed at scheduled intervals. Targeted physical exam based on new and ongoing signs or symptoms at Weeks 4, 8, 12, 18, and 24; weight at Weeks 4, 12, 24; Karnofsky status, urinalysis with microscopic examination, and serum beta-HCG test for women of child-bearing potential at Weeks12 and 24; CBC with MCV, differential and platelets; electrolytes, liver function tests, amylase, alkaline phosphatase and total bilirubin will be done at Weeks 2, 4, 8, 12, 18 and 24. Results and Future Plans: The study is ongoing and treatment arms remain blinded, therefore study conclusions and significance can not yet be discussed. The study is currently closed to accrual, though patients are continuing to be followed. A longer-term follow-up phase is being contemplated.